Inflammatory breast cancer (IBC) is a clinically and pathologically distinct form of locally advanced breast cancer associated with a rapid growth rate and high metastatic potential.Inflammatory and locally advanced breast cancer: Biology, treatment and association with angiogenesis. Research aims: 1) To determine the long-term outcome of patients with inflammatory breast cancer (IBC) and non-IBC treated with multimodality therapy. 2) To evaluate molecular and angiogenic markers in patients with IBC and compare them with markers in patients with non-IBC. 3) To evaluate molecular markers, vascular permeability, and clinical parameters in patients with stage III and IV IBC treated with the anti-angiogenic agent bevacizumab (BV). Accomplishments: A pilot study of BV in patients with IBC completed accrual or 21 patients. There was a significant decrease in tumor-associated phospho-KDR expression, and increase in tumor apoptosis and a decrease in vascular permeability by MRI after BV treatment alone. In responding patients, there were trends toward decreased VEGF expression after BV alone and decreased tumor cell proliferation after BV and chemotherapy.Although the aggressiveness of IBC is well known, there is no clear clinicopathologic profile for this tumor type, often making diagnosis difficult. One goal of our study is to develop a clinicopathological diagnosis of IBC by using the anonymyzed data and correlating it with molecular markers expressed by the tumors. The Inflammatory Breast Cancer Registry and Biospecimen Repository is a project funded by a grant from the Department of Defense to Dr. Paul H. Levine (George Washington University Medical Center - GWUMC). The purpose of the registry is to develop a national registry of patients with IBC that will contain standardized clinical, epidemiological, and pathological information, along with recurrence and survival data. Investigators at GWUMC will consent recruited patients and collect clinical data. We obtained tumor blocks from 132 patients with IBC from the Registry and cut10 slides from each block. We obtained 150 non-IBC stage matched specimens from the Cooperative Breast Cancer Tissue Resource (CBCTR) to be used as control tissue. The hypothesis for the first study is that IBC is a unique disease and consequently expresses multiple unique molecular markers, including those associated with angiogenesis and lymphangiogenesis. We plan to determine whether there are differences in molecular markers between patients with and without IBC. The nine markers to be studied by IHC in collaboration with the MPC, CTB are ER, c-erbB-2, E-cadherin, MVD, Ki67, podoplanin, HIF-1??, VEGF-A, and phospho-KDR. Tissue sections will be evaluated for tumor content using hematoxylin and eosin staining. Dr. Mark Sherman (Division of Cancer Epidemiology and Genetics, NCI), will review all slides for presence of tumor, histology, grade, and lymphovascular invasion which has partially been completed at this time. Preliminary work has been done optimizing the staining for podoplanin. To assess whether angiogenesis could be targeted in the treatment of patients with IBC, we performed a pilot study in patients with previously untreated IBC or LABC to evaluate parameters of angiogenesis after treatment with bevacizumab (BV), a recombinant humanized monoclonal anti-VEGF antibody. To be eligible for the study, patients had to have previously untreated IBC or LABC, good performance status (ECOG status 0-2), good bone marrow, renal, and hepatic functions, and no uncontrolled hypertension, proteinuria or brain metastases. The first cycle of treatment consisted of BV (15 mg/m2) alone, followed by six cycles of BV in combination with doxorubicin (50 mg/m2) and docetaxel (75 mg/m2) given intravenously (IV), and G-CSF. Treatment was given every 3 weeks. Cycle 7 was followed by loco-regional treatment with surgery and radiation therapy.